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CACNA1S calcium voltage-gated channel subunit alpha1 S [ Homo sapiens (human) ]

Gene ID: 779, updated on 3-Apr-2024

Summary

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Official Symbol
CACNA1Sprovided by HGNC
Official Full Name
calcium voltage-gated channel subunit alpha1 Sprovided by HGNC
Primary source
HGNC:HGNC:1397
See related
Ensembl:ENSG00000081248 MIM:114208; AllianceGenome:HGNC:1397
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MHS5; DHPRM; HOKPP; TTPP1; CMYP18; Cav1.1; HOKPP1; hypoPP; CCHL1A3; CACNL1A3
Summary
This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008]
Expression
Biased expression in esophagus (RPKM 1.7), prostate (RPKM 1.6) and 4 other tissues See more
Orthologs
mouse all
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Genomic context

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See CACNA1S in Genome Data Viewer
Location:
1q32.1
Exon count:
44
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (201039512..201112426, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (200296459..200369410, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (201008640..201081554, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2304 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:200945792-200946991 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2305 Neighboring gene kinesin family member 21B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:200969230-200969730 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:200985675-200986222 Neighboring gene Sharpr-MPRA regulatory region 10908 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2306 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2307 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1683 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:200991037-200991644 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1684 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1685 Neighboring gene uncharacterized LOC101929305 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:200993410-200993567 Neighboring gene Sharpr-MPRA regulatory region 14143 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201021057-201021557 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201022145-201023102 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2308 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201028065-201028818 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201031613-201032386 Neighboring gene uncharacterized LOC124904481 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201070239-201070740 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201070741-201071240 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201072987-201073503 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1686 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:201084381-201084901 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:201095506-201096496 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:201096497-201097487 Neighboring gene achaete-scute family bHLH transcription factor 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:201103675-201103881 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2309 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1687 Neighboring gene transmembrane protein 9 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2310

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Short-Communication: Variable Expression of Clinical Symptoms and an Unexpected Finding of Vacuolar Myopathy Related to a Pathogenic Variant in the CACNA1S Gene in a Previous Case Report. Benítez-Alonso EO, et al. Cureus, 2022 Apr. PMID 35509735, Free PMC Article
  2. Malignant Hyperthermia: A Killer If Ignored. Bin X, et al. J Perianesth Nurs, 2022 Aug. PMID 35414440
  3. Analysis of Factors That May Affect the Effectiveness of Ketogenic Diet Treatment in Pediatric and Adolescent Patients. Winczewska-Wiktor A, et al. J Clin Med, 2022 Jan 25. PMID 35160058, Free PMC Article
  4. Novel CACNA1S mutation in hypokalaemic periodic paralysis. Luís T, et al. BMJ Case Rep, 2022 Jan 17. PMID 35039355, Free PMC Article
  5. Vacuolar Myopathy Associated to CACNA1S Mutation as a Rare Cause of Late-Onset Limb-Girdle Myopathy: A Case Report. López-Hernández JC, et al. Cureus, 2021 Oct. PMID 34804722, Free PMC Article

See all (100) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Biallellic variants in CACNA1S cause fetal akinesia sequence, progressive hydrops and stillbirth.
    Title: Biallellic variants in CACNA1S cause fetal akinesia sequence, progressive hydrops and stillbirth.
  2. CACNA1S Variant Associated With a Myalgic Myopathy Phenotype.
    Title: CACNA1S Variant Associated With a Myalgic Myopathy Phenotype.
  3. Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature.
    Title: Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature.
  4. Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.
    Title: Mutations associated with hypokalemic periodic paralysis: from hotspot regions to complete analysis of CACNA1S and SCN4A genes.
  5. MRTF-A regulates Ca(2+) release through CACNA1S.
    Title: MRTF-A regulates Ca(2+) release through CACNA1S.
  6. Gating pore currents occur in CaV1.1 domain III mutants associated with HypoPP.
    Title: Gating pore currents occur in CaV1.1 domain III mutants associated with HypoPP.
  7. Structural determinants of voltage-gating properties in calcium channels.
    Title: Structural determinants of voltage-gating properties in calcium channels.
  8. Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
    Title: Mutation spectrum and health status in skeletal muscle channelopathies in Japan.
  9. Investigating the genetic susceptibility to exertional heat illness.
    Title: Investigating the genetic susceptibility to exertional heat illness.
  10. Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene.
    Title: Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene.
Submit: New GeneRIF Correction See all GeneRIFs (50)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in CACNA1S that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated 2016-01-18)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated 2016-01-18)

ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genome-wide association study identifies four loci associated with eruption of permanent teeth.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calmodulin binding IEA
Inferred from Electronic Annotation
more info
  
enables high voltage-gated calcium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables high voltage-gated calcium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables molecular function activator activity EXP
Inferred from Experiment
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables small molecule binding EXP
Inferred from Experiment
more info
 PubMed 
enables voltage-gated calcium channel activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables voltage-gated calcium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium ion import across plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in calcium ion transmembrane transport NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in calcium ion transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to caffeine ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in endoplasmic reticulum organization IEA
Inferred from Electronic Annotation
more info
  
involved_in extraocular skeletal muscle development IEA
Inferred from Electronic Annotation
more info
  
involved_in muscle contraction IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in myoblast fusion IEA
Inferred from Electronic Annotation
more info
  
involved_in neuromuscular junction development IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of muscle contraction NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in release of sequestered calcium ion into cytosol IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in skeletal muscle adaptation IEA
Inferred from Electronic Annotation
more info
  
involved_in skeletal muscle fiber development IEA
Inferred from Electronic Annotation
more info
  
involved_in skeletal system development IEA
Inferred from Electronic Annotation
more info
  
involved_in striated muscle contraction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in I band IDA
Inferred from Direct Assay
more info
 PubMed 
part_of L-type voltage-gated calcium channel complex ISO
Inferred from Sequence Orthology
more info
  
part_of L-type voltage-gated calcium channel complex ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in T-tubule IDA
Inferred from Direct Assay
more info
 PubMed 
located_in T-tubule IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in sarcoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
part_of voltage-gated calcium channel complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of voltage-gated calcium channel complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
voltage-dependent L-type calcium channel subunit alpha-1S
Names
calcium channel, voltage-dependent, L type, alpha 1S subunit
dihydropyridine receptor alpha 1 subunit
dihydropyridine-sensitive L-type calcium channel alpha-1 subunit
voltage-gated calcium channel subunit alpha Cav1.1

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009816.2 RefSeqGene

    Range
    5141..78055
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000069.3 → NP_000060.2  voltage-dependent L-type calcium channel subunit alpha-1S

    See identical proteins and their annotated locations for NP_000060.2

    Status: REVIEWED

    Source sequence(s)
    AL139159, AL358473
    Consensus CDS
    CCDS1407.1
    UniProtKB/Swiss-Prot
    A4IF51, B1ALM2, Q12896, Q13698, Q13934
    UniProtKB/TrEMBL
    A0A7P0T8M7
    Related
    ENSP00000355192.3, ENST00000362061.4
    Conserved Domains (5) summary
    pfam00520
    Location:1135 → 1392
    Ion_trans; Ion transport protein
    pfam05104
    Location:671 → 777
    Rib_recp_KP_reg; Ribosome receptor lysine/proline rich region
    pfam08763
    Location:1465 → 1536
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16885
    Location:1692 → 1833
    CAC1F_C; Voltage-gated calcium channel subunit alpha, C-term
    pfam16905
    Location:1400 → 1463
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    201039512..201112426 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005245478.4 → XP_005245535.1  voltage-dependent L-type calcium channel subunit alpha-1S isoform X1

    UniProtKB/TrEMBL
    A0A7P0T8M7, B1ALM3
    Related
    ENSP00000356307.3, ENST00000367338.7
    Conserved Domains (5) summary
    pfam00520
    Location:1135 → 1373
    Ion_trans; Ion transport protein
    pfam05104
    Location:671 → 777
    Rib_recp_KP_reg; Ribosome receptor lysine/proline rich region
    pfam08763
    Location:1446 → 1517
    Ca_chan_IQ; Voltage gated calcium channel IQ domain
    pfam16885
    Location:1673 → 1814
    CAC1F_C; Voltage-gated calcium channel subunit alpha, C-term
    pfam16905
    Location:1381 → 1444
    GPHH; Voltage-dependent L-type calcium channel, IQ-associated

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    200296459..200369410 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054338645.1 → XP_054194620.1  voltage-dependent L-type calcium channel subunit alpha-1S isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13698.4 GenPept UniProtKB/Swiss-Prot:Q13698

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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